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In recent years, there has been growing scientific interest in balancing the bioactivity and cytotoxicity of antimicrobial peptides (AMPs) for more comprehensive research and application. In this study, we focused on t-DPH1, a representative member of the dermaseptin family, as a template. We synthesized five analogues were synthesised to to assess the impact of three conserved features of the dermaseptin family (1. the tryptophan residue at 3rd position, 2. the consensus motif at mid-region, and 3. C-terminal amidation) on the bioactivity of t-DPH1 and their potential to reduce cytotoxicity. Our results demonstrated that analogues lacking an amino group at the C-terminus, specifically t-DPH1-NH2, exhibited potent antimicrobial activity against Gram-negative bacteria, including Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae). Furthermore, t-DPH1-NH2 retained its robust antiproliferative activity against the human non-small lung cancer cell line H157. Regarding cytotoxicity, t-DPH1-NH2 displayed lower levels of haemolytic activity and cytotoxicity against two normal cell lines. Notably, we employed C. elegans as an in vivo model to assess the cytotoxicity of peptides, and the results revealed no induction of in vivo toxicity by t-DPH1-NH2. Collectively, t-DPH1-NH2 provides valuable insights for further investigation as promising bioactive peptide templates in the development of antibiotic and anticancer prototype drugs. The modifications implemented based on the conserved structure of the peptide family offer a new direction for reducing the cytotoxicity of peptides.

Documents have revealed that leaves, barks and woods from oak trees are rich in phenols, yet little is known about them in Mongolian oak (Quercus mongolica) cups, the by-product waste with large biomass. In the present work, composition analysis through total phenols, flavonoids and tannins, and condensed tannins, and HPLC profiles and antioxidant assessment by DPPH, ABTS, reducing power, ORAC and CAA were performed to evaluate oak cup crude extracts and the resulting four fractions (Fr. I, Fr. II, Fr. III and Fr. IV) prepared by HPD-100 macroporous resin chromatography. Among the optimal 50% ethanol crude extract (ECE) and its subsequent four fractions, Fr. II, on the basis of the oak cups, collected the majority of total phenols, flavonoids and tannins, and condensed tannins from ECE though lower contents of all compositions than those in Fr. III when based on the extract with an exception of condensed tannins. And the highlight of Fr. II is that it possessed the strongest antioxidant ability from the perspective of extract. These findings imply that composition of condensed tannins as well as its contents might take dominate role in antioxidant ability of oak cups. This was further corroborated through HPLC profiles as compositions in ECE and the four fractions are all distinguished from each other. HPLC also exhibited the great enrichment of ellagic acid in Fr. III. Moreover, the correlation analysis indicated that there is exclusive correlation existed between total flavonoids and antioxidant assays among all composition analysis including ellagic acid, which further confirmed the main influencing factor to antioxidant ability of oak cup may be composition of condensed tannins as well as its contents because the condensed tannins were constituted by flavonoid units, and ellagic acid may not be a strong antioxidant contributor in oak cups. Therefore, Fr. II should be chosen as the best fraction to be further explored. In addition, this established HPD-100 macroporous resin chromatography procedure could be developed as a simple and effective procedure for preparation of ellagic acid from oak cups. Keywords: Mongolian oak (Quercus mongolica) cups, Flavonoids, Condensed tannins, Antioxidant activities, Macroporous resin, HPLC

Abstract A flavonoids-rich extract of Scutellaria baicalensis shoots and its eight high content flavonoids were investigated for their inhibitory effects against α-glucosidase and α-amylase. Results show that abilities of the extract in inhibiting the two enzymes were obviously higher than those of acarbose. Moreover, inhibitory abilities of all the eight individual flavonoids against the two enzymes show exactly a same order (i.e., apigenin > baicalein > scutellarin > chrysin > apigenin-7-O-glucuronide > baicalin > chrysin-7-O-glucuronide > isocarthamidin-7-O-glucuronide), and their structure–activity relationship could be well-interpretated by the refined assign-score method. Furthermore, based on the inhibitory abilities and their contents in the extract, it was found that the eight flavonoids made predominant contributions, among which baicalein and scutellarin played roles as preliminary contributors, to overall inhibitory effects of the extract against the two enzymes. Beyond these, contributions of the eight flavonoids to the overall enzyme inhibitory activity were compared with those to the overall antioxidant activity characterized in our recent study, and it could be inferred that within the basic flavonoid structure the hydroxyl on C-4′ of ring B was more effective than that on C-6 of ring A in enzyme inhibitory activities while they behaved inversely in antioxidant activities; scutellarin and apigenin contributed more to the overall enzyme inhibitory activity, and baicalin and scutellarin, to the overall antioxidant activity of the extract; and flavonoids of the extract, apart from directly inhibiting enzymes, might also be conducive to curing type 2 diabetes via scavenging various free radicals caused by increased oxidative stresses.

Investigation of flavonoids-rich extract from Scutellaria baicalensis shoots shows that 15 of the 19 flavonoids detected with UPLC-Q-TOF-MS were identified, and it exhibited high antioxidant abilities with IC50 at 70.81, 35.34 and 33.27 μg/mL in DPPH, ABTS and CAA assays, respectively. An order of antioxidant abilities in scavenging DPPH· and ABTS+· of eight high content flavonoids in the extract was the same, and it could be well-explained by a preliminary assign-score method we created in structure-activity relationship analyses specific for flavonoids, revealing that double bonds and phenolic hydroxyls on rings A and B are augmentors, and sugar moiety is an attenuator influencing antioxidant capacity but might contribute positively in CAA assays. In addition, three of the eight flavonoids (baicalein, baicalin and scutellarin) made contributions of 58.33%, 60.36% and 51.41% to overall antioxidant activity of the flavonoids-rich extract in DPPH, ABTS and CAA assays, respectively, thus were determined as the primary or marker flavonoids of Scutellaria baicalensis shoots.

Acer truncatum leaves (ATL) have long been used in China as a substitutional tea with health benefits. However, little is known about the antioxidant capacities as well as its bioactive components. The present study was to investigate constitutive phenolic compositions and evaluate antioxidant activities of ATL through its whole growing season. The results showed that all seasonal ATL samples contained remarkable phenols, tannins and flavonoids, and exhibited high antioxidant capacities. Constitutive levels of total phenols, tannins and flavonoids, and three individual phenolic compounds, namely 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), methyl gallate (MG), and quercetin-3-O-l-rhamnoside (QR), and DPPH· and ABTS+· scavenging capacities were all significantly higher in both the beginning (S4) and ending (S11) months than those in the middle months (S5–S10), resulting in a consistent seasonal saddle-shaped pattern. Since S4 and S11 showed significant differences in oxygen radical absorbance capacity (ORAC) values but not in total flavonoids, and there was no significant correlation between ORAC and total flavonoids, it can be inferred that total flavonoids contributed less to the ORAC values than total phenols and tannins did. Correlation analyses further revealed that total phenols, tannins and flavonoids were the main contributors to antioxidant ability, and PGG, MG and QR were found to be the key components of phenols (including tannins and flavonoids) in ATL. Gallic acid was first discovered in ATL, and high levels of PGG and QR (both higher than 1 g/100 g d.w. in April) were corroborated through HPLC analysis. Impressive antioxidant abilities of S4 and S11 were further demonstrated by cellular antioxidant assay, and flavonoids showed stronger antioxidant capacity in the cellular level than other phenolic compositions. In conclusion, seasonal dynamics of constitutive levels of phenolic components lead to alterations of antioxidant capacities in ATL, and November and April were the ideal harvesting time with highest levels of phenols and antioxidant capacity.

Temporin is an antimicrobial peptide (AMP) family discovered in the skin secretion of ranid frog that has become a promising alternative for conventional antibiotic therapy. Herein, a novel temporin peptide, Temporin-PF (TPF), was successfully identified from Pelophylax fukienensis. It exhibited potent activity against Gram-positive bacteria, but no effect on Gram-negative bacteria. Additionally, TPF exhibited aggregation effects in different solutions. Three analogs were further designed to study the relationship between the aggregation patterns and bioactivities, and the MD simulation was performed for revealing the pattern of the peptide assembly. As the results showed, all peptides were able to aggregate in the standard culture media and salt solutions, especially CaCl2 and MgCl2 buffers, where the aggregation was affected by the concentration of the salts. MD simulation reported that all peptides were able to form oligomers. The parent peptide assembly depended on the hydrophobic interaction via the residues in the middle domain of the sequence. However, the substitution of Trp/D-Trp resulted in an enhanced inter-peptide interaction in the zipper-like domain and eliminated overall biological activities. Our study suggested that introducing aromaticity at the zipper-like domain for temporin may not improve the bioactivities, which might be related to the formation of aggregates via the inter-peptide contacts at the zipper-like motif domain, and it could reduce the binding affinity to the lipid membrane of microorganisms.

Ultra-short-term wind power prediction is of great importance for the integration of renewable energy. It is the foundation of probabilistic prediction and even a slight increase in the prediction accuracy can exert significant improvement for the safe and economic operation of power systems. However, due to the complex spatiotemporal relationship and the intrinsic characteristic of nonlinear, randomness and intermittence, the prediction of regional wind farm clusters and each wind farm’s power is still a challenge. In this paper, a framework based on graph neural network and numerical weather prediction (NWP) is proposed for the ultra-short-term wind power prediction. First, the adjacent matrix of wind farms, which are regarded as the vertexes of a graph, is defined based on geographical distance. Second, two graph neural networks are designed to extract the spatiotemporal feature of historical wind power and NWP information separately. Then, these features are fused based on multi-modal learning. Third, to enhance the efficiency of prediction method, a multi-task learning method is adopted to extract the common feature of the regional wind farm cluster and it can output the prediction of each wind farm at the same time. The cases of a wind farm cluster located in Northeast China verified that the accuracy of a regional wind farm cluster power prediction is improved, and the time consumption increases slowly when the number of wind farms grows. The results indicate that this method has great potential to be used in large-scale wind farm clusters.

Retinal ischemia contributes to visual impairment in ischemic retinopathies. A disintegrin and metalloproteinase ADAM17 is implicated in multiple vascular pathologies through its ability to regulate inflammatory signaling via ectodomain shedding. We investigated the role of endothelial ADAM17 in neuronal and vascular degeneration associated with retinal ischemia reperfusion (IR) injury using mice with conditional inactivation of ADAM17 in vascular endothelium. ADAM17Cre-flox and control ADAM17flox mice were subjected to 40 min of pressure-induced retinal ischemia, with the contralateral eye serving as control. Albumin extravasation and retinal leukostasis were evaluated 48 h after reperfusion. Retinal morphometric analysis was conducted 7 days after reperfusion. Degenerate capillaries were assessed by elastase digest and visual function was evaluated by optokinetic test 14 and 7 days following ischemia, respectively. Lack of ADAM17 decreased vascular leakage and reduced retinal thinning and ganglion cell loss in ADAM17Cre-flox mice. Further, ADAM17Cre-flox mice exhibited a remarkable reduction in capillary degeneration following IR. Decrease in neurovascular degeneration in ADAM17Cre-flox mice correlated with decreased activation of caspase-3 and was associated with reduction in oxidative stress and retinal leukostasis. In addition, knockdown of ADAM17 resulted in decreased cleavage of p75NTR, the process known to be associated with retinal cell apoptosis. A decline in visual acuity evidenced by decrease in spatial frequency threshold observed in ADAM17flox mice was partially restored in ADAM17-endothelial deficient mice. The obtained results provide evidence that endothelial ADAM17 is an important contributor to IR-induced neurovascular damage in the retina and suggest that interventions directed at regulating ADAM17 activity can be beneficial for alleviating the consequences of retinal ischemia.

Engagement of programmed death-ligand 1 (PD-L1) with its receptor programmed death 1 (PD-1) on T cells has been speculated to play a major role in suppressing the immune system, which helps tumor cells evade anti-tumor immunity. With the development of whole genome sequencing technologies, microRNAs have gained more attention as an important new layer of molecular regulation. Recent studies have revealed that altered expression of microRNAs play a pivotal role in immune checkpoint and various cellular processes in cancer. In this review, we focused on the latest progress about microRNAs research which involves the regulation of PD-1/PD-L1 immune checkpoint.